Abstract 6002: Invasiveness-dependent mechanical plasticity of cancer cells
Authors: Xingyu Xia, Zishen Yan, William C. Cho, Yuan Lin
Journal: Cancer Research (2022)

Abstract Introduction: The capability of living cells to undergo deformations is critical for them to perform different biological functions, such as migration, spreading and endocytosis. Interestingly, recent evidence has also suggested that the mechanical response of cancer cells is intimately related to their pathological state. Physically, a reduced modulus will make it easier for cancer cells to change their morphology when squeezing through tight endothelial cell-cell junctions or pores in the extracellular matrix. However, the deformed cell will fully restore to its original shape if the response is purely elastic or viscoelastic. In this regard, the capability of cells to retain irreversible deformations, and hence effectively “memorize” the characteristics of the physical confinement that they have encountered, could greatly facilitate their subsequent passage through similar barriers, which is a common scenario in tumor cell invasion and metastasis. Here, we developed a method, for the first time to the best of our knowledge, to quantitatively measure the apparent plastic response of tumor cells and examine its correlation with their invasiveness. Materials and Methods: A microfluidic device was designed to deform the cell and then extract its viscoelastic and plastic characteristics from its shape recovery. The chip was casted by molding of silicon wafer which was fabricated using photo etching method. During the test, cells were pushed to squeeze through the deformation channel of the chip. Deformations of the cell and its nucleus were monitored under a fluorescent microscope. Two breast cancer cell lines (MDA-MB-231 and MCF-7), one nasopharyngeal cell line (NP69), and one carcinoma counterpart (HONE-1) were used. To verify the correlation of plastic response with cytoskeleton damage, Latrunculin A was added to block F-actin formation. SYTO fluorescent dye was used for live imaging of the cell nucleus. Results: After being deformed in the narrow channel for a few seconds, cells were released free and recovered the deformation. Interestingly, the highly invasive MDA-MB-231 and HONE-1 cells underwent irreversible deformation even after 10 minutes. However, NP69 and the poorly invasive MCF-7 cells fully recovered to the original round shape in a few minutes. But after blocking the F-actin formation with Latrunculin A, MCF-7 cells retained partial plastic strain. The nucleus elongated when the cell deformed, but fully recovered in 5 minutes. The results indicated the irreversible deformation of cells originated from cytoskeleton damage, but not the nucleus deformation. Conclusions: No apparent irreversible deformation was observed in the less invasive cell lines, suggesting that the plastic response of tumor cells might be correlated with their invasiveness. In addition, it was found that the plastic deformation of highly invasive cancer cells is caused by their cytoskeleton damage rather than plasticity of the nucleus. Citation Format: Xingyu Xia, Zishen Yan, William C. Cho, Yuan Lin. Invasiveness-dependent mechanical plasticity of cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6002.